title: Diagnostic utility and limitations of glutamine synthetase and serum amyloid-associated protein immunohistochemistry in the distinction of focal nodular hyperplasia and inflammatory hepatocellular adenoma.
abstract: Inflammatory hepatocellular adenoma can show overlapping histological features with focal nodular hyperplasia, including inflammation, fibrous stroma, and ductular reaction. Expression of serum amyloid-associated protein in inflammatory hepatocellular adenoma and map-like pattern of glutamine synthetase in focal nodular hyperplasia can be helpful in this distinction, but the pitfalls and limitations of these markers have not been established. Morphology and immunohistochemistry were analyzed in 54 inflammatory hepatocellular adenomas, 40 focal nodular hyperplasia, and 3 indeterminate lesions. Morphological analysis demonstrated that nodularity, fibrous stroma, dystrophic blood vessels, and ductular reaction were more common in focal nodular hyperplasia, while telangiectasia, hemorrhage, and steatosis were more common in inflammatory hepatocellular adenoma, but there was frequent overlap of morphological features. The majority of inflammatory hepatocellular adenomas demonstrated perivascular and/or patchy glutamine synthetase staining (73.6%), while the remaining cases had diffuse (7.5%), negative (3.8%), or patchy pattern of staining (15%) that showed subtle differences from the classic map-like staining pattern and was designated as pseudo map-like staining. Positive staining for serum amyloid-associated protein was seen in the majority of inflammatory hepatocellular adenomas (92.6%) and in the minority of focal nodular hyperplasia (17.5%). The glutamine synthetase staining pattern was map-like in 90% of focal nodular hyperplasia cases, with the remaining 10% of cases showing pseudo map-like staining. Three cases were labeled as indeterminate and showed focal nodular hyperplasia-like morphology but lacked map-like glutamine synthetase staining pattern; these cases demonstrated a patchy pseudo map-like glutamine synthetase pattern along with the expression of serum amyloid-associated protein. Our results highlight the diagnostic errors that can be caused by variant patterns of staining with glutamine synthetase and serum amyloid-associated protein in inflammatory hepatocellular adenoma and focal nodular hyperplasia.
authors.affiliation: Department of Anatomic Pathology, University of California, San Francisco, CA, USA.
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Joseph
authors.affiliation: Department of Anatomic Pathology, University of California, San Francisco, CA, USA.
authors.forename: Linda D
authors.initials: LD
authors.lastname: Ferrell
authors.affiliation: Department of Pathology, Yale University, New Haven, CT, USA.
authors.forename: Dhanpat
authors.initials: D
authors.lastname: Jain
authors.affiliation: Department of Pathology, Johns Hopkins, Baltimore, MD, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Torbenson
authors.affiliation: Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Tsung-Teh
authors.initials: TT
authors.lastname: Wu
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Yeh
authors.affiliation: 1] Department of Anatomic Pathology, University of California, San Francisco, CA, USA [2] Department of Anatomic Pathology, University of California and Veteran Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kakar
mesh_terms: D018248:Adenoma, Liver Cell / Q000737:chemistry / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002097:C-Reactive Protein / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D003951:Diagnostic Errors; D005260:Female; D020518:Focal Nodular Hyperplasia / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D005974:Glutamate-Ammonia Ligase / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis; D008113:Liver Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D000685:Serum Amyloid A Protein / Q000032:analysis*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018836:Inflammation Mediators; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein; D005974:Glutamate-Ammonia Ligase